D. A. Ferreira

Performance of electroencephalogram-derived parameters in prediction of depth of anaesthesia in a rabbit model

BACKGROUND The index of consciousness (IoC), the permutation entropy (PE), and the approximate entropy are recent EEG-derived indices of anaesthetic depth. In this study, a rabbit model under fentanyl and isoflurane anaesthesia was used to compare the performance of these indices and also the classic median and spectral edge frequency 95%. METHODS EEG recordings were obtained from six rabbits. Animals received fentanyl for premedication, followed by induction with propofol and maintenance with isoflurane. Anaesthetic depth was evaluated according to a clinical scale from 1 (awake) to 4 (surgical anaesthesia). Animals were submitted to surgical implantation of a small device in the lumbar muscles. A correction factor for the EEG suppression ratio was applied to the spectral parameters and to the PE. The correlation of the indices with the clinical scale of anaesthesia was analysed using prediction probability. Repeated-measures analysis of variance or its non-parametric equivalent was used to analyse the indices values at the study times and to compare their variability. RESULTS The IoC showed the best mean prediction probability value [0.94 (0.01)] followed by burst suppression-corrected PE [0.91(0.03)]. Both parameters also showed less variability than the others. CONCLUSIONS The IoC and PE are promising indices for anaesthetic depth monitoring. The PE might benefit from the application of a burst suppression correction at deeper stages of anaesthesia. The rabbit is useful as a translational research animal model for the validation of clinical indices.

The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuli.

Background and objective: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. Methods: ASA I–III patients were included in this study. All patients received a 2 μg k g−1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A‐2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30‐s period and analysed using analysis of variance. Results: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P < 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 ± 19.9 mmHg at the time of the bolus to 74.2 ± 16.6 mmHg 120 s after, and from 70 ± 16.4 bpm at the time of the bolus to 61 ± 13.6 bpm after (P < 0.001), respectively. Conclusions: There was a significant reduction in the areas under the curve between 90–120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures.

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 μg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean ± SD. Effect-site propofol concentration at ROC was 1.3 ± 0.5 μg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 ± 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 ± 0.05 μg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 ± 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 ± 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 ± 6.8), time till minimum BIS (4.7 ± 2.2 min), mean and median BIS during surgery (38.2 ± 4.5 and 37.8 ± 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.

A step towards effect‐site target‐controlled infusion with propofol in dogs: a ke0 for propofol

Target-controlled infusion (TCI) anesthesia using target effect-site concentration rather than plasma concentration provides less drug consumption, safer anesthesia, less undesired side effects and improved animal welfare. The aim of this study was to calculate the constant that converts propofol plasma into effect-site concentration (k(e0)) in dogs, and to implement it in a TCI system and compare it with the effect on the central nervous system (CNS). All dogs were subjected to general anesthesia using propofol. Fourteen dogs were used as the pilot group to calculate k(e0), using the t(peak) method. Fourteen dogs were used as the test group to test and validate the model. RUGLOOP II software was used to drive the propofol syringe pump and to collect data from S/5 Datex monitor and cerebral state monitor. The calculated k(e0) was incorporated in an existing pharmacokinetic model (Beths Model). The relationship between propofol effect site concentrations and anesthetic planes, and propofol plasma and effect-site concentrations was compared using Pearsons correlation analysis. Average t(peak) was 3.1 min resulting in a k(e0) of 0.7230 min(-1). The test group showed a positive correlation between anesthetic planes and propofol effect-site concentration (R = 0.69; P < 0.0001). This study proposes a k(e0) for propofol with results that demonstrated a good adequacy for the pharmacokinetic model and the measured effect. The use of this k(e0) will allow an easier propofol titration according to the anesthetic depth, which may lead to a reduction in propofol consumption and less undesired side effects usually associated to high propofol concentrations in dogs.

Modelling the dynamics of depth of anaesthesia: Cerebral state index in dogs

The goal of this study was to obtain models that described the relation between the anaesthetic drug infusions (propofol) and an electroencephalogram (EEG) derived index (Cerebral State Index -CSI) during general anaesthesia in dogs. The first phase integrated the adaptation of hardware for EEG acquisition and exploration for the best electrodes position in dogs skull. The clinical protocol implementation and data collection were the next steps followed by CSI modeling. CSI showed adequate response to changes in drug infusion, reflecting the changes of depth of anaesthesia in dogs. The models obtained adjusted well to the original CSI data and also predicted the CSI trend during surgery. Using this monitor in current practice might improve quality in the anaesthesia procedure providing a useful tool to administer a correct sedation.

Synchronization Software for Automation in Anesthesia

This work presents the development of a software for data acquisition and control (ASYS) on a clinical setup. Similar to the industrial Supervisory Control And Data Acquisition (SCADA) the software assembles a target controlled infusion (TCI) monitoring and supervisory control data in real time from devices in a surgical room. The software is not a full controller since the TCI systems comprehend permanent interaction from the anesthesiologist. Based on pharmacokinetic models, the effect-site and plasma concentrations can be related with the drug dose infused and vice versa. The software determines the infusion rates of the drug which are given as commands to the infusion pumps. This software provides the anesthesiologist with a trustworthy tool for managing a safe and balanced anesthesia. Since it also incorporates the acquisition and display of patients brain signals.

Brain tumors may alter the relationship between bispectral index values and propofol concentrations during induction of anesthesia

STUDY OBJECTIVE To compare propofol-predicted effect-site concentrations (PropCe) and bispectral index (BIS) of the electroencephalogram during induction of anesthesia in patients with small brain tumors and to analyze BIS and PropCe at loss of consciousness (LOC). DESIGN Prospective investigation. SETTING Operating theater of a university hospital. PATIENTS 26 ASA physical status I and II patients, 13 of whom were scheduled for nontumor spinal surgeries, and the other 13, for brain surgery for small brain tumor removal. INTERVENTIONS Anesthesia was induced with a propofol 1% constant infusion rate of 200 mL/h until LOC. MEASUREMENTS BIS, PropCe, heart rate, and mean arterial pressure were analyzed at the beginning of the propofol infusion and every 30 seconds during induction. MAIN RESULTS The BIS values were significantly higher in patients with brain tumors in the period from 150 to 210 seconds, with PropCe similar to patients without brain tumors. Loss of consciousness occurred 3.6 +/- 0.8 minutes in patients without brain tumors and 3.9 +/- 0.7 minutes in patients with brain tumors. No differences were observed between groups in the time to LOC (3.6 +/- 0.8 in group 1 vs 3.9 +/- 0.7 in group 2) or in BIS at LOC (48.7 +/- 11.4 in group 1 vs 58.6 +/- 21.7 in group 2). CONCLUSIONS For similar propofol concentrations, patients with small brain tumors show higher BIS values on induction of anesthesia with propofol.

Comparison of Neural Networks, Fuzzy and Stochastic Prediction Models for return of consciousness after general anesthesia

This paper presents three modeling techniques to predict return of consciousness (ROC) after general anesthesia, considering the effect concentration of the anesthetic drug at awakening. First, several clinical variables were statistically analysed to determine their correlation with the awakening concentration. The anesthetic and the analgesic mean dose during surgery, and the age of the patient, proved to have significantly high correlation coefficients. Variables like the mean bispectral index value during surgery, duration of surgery did not present a statistical relation with ROC. Stochastic regression models were built using the variables with higher correlation. Secondly, fuzzy models were built using an Adaptive Network-Based Fuzzy Inference System (ANFIS) also relating different sets of variables. Thirdly, radial basis function (RBF) neural networks were trained relating different sets of clinical values with the anesthetic drug effect concentration at awakening. Clinical data was used to train and test the models. The stochastic models and the fuzzy models proved to have good prediction properties. The RBF network models were more biased towards the training set. The best balanced performance was achieved with the fuzzy models.

The effect of high doses of remifentanil in brain near- infrared spectroscopy and in electroencephalographic parameters in pigs

OBJECTIVE To study the effects of a high remifentanil bolus dose on pigs electroencephalographic indices and on brain regional and global oxygenation. STUDY DESIGN Prospective experimental study. ANIMALS Twelve healthy Large-White male pigs, age 3 months and weight 26.2 ± 3.6 kg. METHODS Anaesthesia was induced with intravenous propofol 4 mg kg⁻¹, then maintained with constant rate infusions of propofol (15 mg kg⁻¹ hour⁻¹) and remifentanil (0.3 μg kg⁻¹ minute⁻¹). Following instrumentation, all pigs received a 5 μg kg⁻¹ remifentanil bolus. The responses of jugular venous oxygen saturation, cardiac output and cerebral oxygen saturation to the remifentanil bolus were studied. The Bispectral index, spectral edge frequency 95%, total power, approximate entropy and permutation entropy were also studied. Repeated measures anova and Pearson correlation were used to analyze the effect of remifentanil bolus on these variables until 5 minutes after the bolus. RESULTS Cardiac output and cerebral oxygen saturation decreased significantly after the remifentanil bolus from 4.6 ± 0.9 to 3.8 ± 1.0 L minute⁻¹ and from 65 ± 6 to 62 ± 1% (p < 0.05), respectively. No significant changes were observed in the jugular venous oxygen saturation (p > 0.05) nor in any of the electroencephalogram derived indices (p > 0.05). Correlation analysis revealed strong positive significant correlations between cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE The effect caused by the remifentanil bolus on the brain oxygenation seems to be better reflected by the cerebral oxygen saturation than the jugular venous oxygen saturation. The effect of remifentanil on the electroencephalogram may not be reflected in indices derived from the electroencephalogram, but the potential of the approximate entropy in reflecting changes caused by opioids on the electroencephalogram should be further investigated.

Interaction between hydroxyethyl starch and propofol: computational and laboratorial study

Background: Hydroxyethyl starch (HES) is one of the most used colloids for intravascular volume replacement during anesthesia. Aim: To investigate the existence of a chemical interaction between HES and the anesthetic propofol by in vitro propofol dosing, computational docking, and examination of a complex between propofol and HES by infrared (IR), ultraviolet (UV), and 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Methods: Ten samples with human plasma mixed with HES or lactated Ringers (n = 5 for each fluid) were prepared, and the propofol free fraction was quantified until 50 min, using gas chromatography-mass spectrometry. The docking study was performed between HES and propofol and compared with controls. The binding affinities between HES and the small molecules were evaluated by binding free energy approximation (ΔGb, kJ mol−1). The IR, UV, and NMR spectra were measured for propofol, HES, and a mixture of both obtained by the kneading method. Results: Propofol concentrations were significantly lower in the HES samples than in the LR samples (p = .021). The spectroscopic characterization of propofol combined with HES revealed differences in spectra and docking studies reinforced a potential interaction between propofol and HES. Conclusions: Propofol and HES form a complex with different physical-bio-chemical behavior than the single drugs, which may be an important drug interaction. Further studies should evaluate its clinical effects.